Source: Based on [52].
Yan and co‐workers developed the intramolecular [4+2] cycloaddition between in situ generated vinylidene ortho‐quinone methides 20 and benzofurans (Scheme 3.30) [53]. In the reaction processes, cinchona alkaloid‐thiourea catalyst 2t promoted the enantioselective prototropic rearrangement (tautomerization) of a 2‐alkynyl naphthol to generate axially chiral vinylidene ortho‐quinone methide 20. Subsequently, the formal inverse electron‐demand hetero‐Diels‐Alder reaction of the vinylidene ortho‐quinone methide with a benzofuran, driven by both rearomatization and strain release, occurred to provide the cycloaddition product. The same group later achieved the enantioselective construction of axially chiral styrenes based on the strategy utilizing the catalytic generation of axially chiral vinylidene ortho‐quinone methides by using chiral acid–base bifunctional catalysts [54].
Scheme 3.30. Intramolecular [4+2] cycloaddition between in situ generated vinylidene ortho‐quinone methides and benzofurans.
Source: Based on [53].
3.3. CHIRAL GUANIDINE CATALYSTS
Guanidine is present in a variety of natural products and plays a key role in many biological activities. It can also be found as the side chain of arginine, one of natural amino acids. The intrinsic and distinctive property of guanidine is its strong basicity resulting from the resonance stability in its conjugate acid form, namely guanidinium cation, in which the positive charge can be delocalized over the three nitrogen atoms. In addition, guanidinium cation can interact strongly with anionic species through the combination of hydrogen bonding and ionic bonding, which is widely utilized in molecular recognition [55]. Because of such characteristic features of guanidine and guanidinium cation, chiral guanidine has attracted considerable attention as a promising platform for chiral Brønsted base catalysts in the field of asymmetric synthesis. Indeed, a variety of chiral guanidine catalysts has been developed, and, as a result, various types of useful enantioselective transformations including carbon–carbon bond formations and carbon‐heteroatom bond formations have been accomplished over the past two decades, which are comprehensively summarized in the literature based on the types of transformations or those of catalysts [4]. Following are the representative chiral guanidine catalysts with their fundamental and/or remarkable applications.
As a pioneering study of chiral guanidine as a chiral Brønsted catalyst, in 1994, Nájera and co‐workers reported the enantioselective nitroaldol reaction albeit with only a modest enantioselectivity [56]. On the other hand, the first highly enantioselective reaction was reported by Lipton and co‐workers in 1996 [57]. They developed the enantioselective Strecker reaction catalyzed by chiral guanidine 21 (Scheme 3.31).
Scheme 3.31. Enantioselective Strecker reaction catalyzed by 21. Source: Based on [57].
In 1999, Corey and Grogan developed the enantioselective Strecker reaction catalyzed by chiral bicyclic guanidine 22a, which is the important seminal work in the field of chiral guanidine catalysis (Scheme 3.32) [58].
Scheme 3.32. Enantioselective Strecker reaction catalyzed by 22a.
Source: Based on [58].
In the report, the authors proposed the suggestive reaction mechanism (Figure 3.8). First, the deprotonation of hydrogen cyanide (HCN) by the guanidine proceeds to form the guanidinium cyanide complex. The complex can function as a hydrogen bond donor, and thus the activation of the imine electrophile occurs to form the pretransition‐state termolecular assembly. Finally, the attack of the cyanide within the ion pair to the hydrogen bond‐activated imine occurs to afford the adduct.
Figure 3.8. Proposed reaction mechanism.
Tan and co‐workers intensively studied the enantioselective transformations by using this type of chiral bicyclic guanidines 22, and successfully developed a lot of highly enantioselective reactions [59]. For instance, a series of enantioselective reactions of anthrones, such as the Diels‐Alder reaction with maleimide and the addition to Michael acceptors, was developed [60]. The tandem reaction process involving a Michael addition of thiols followed by a highly enantioselective protonation was also established by using tert‐butyl substituted 22b (Scheme 3.33) [61].
Scheme 3.33. Enantioselective protonation catalyzed by 22b.
Source: Based on [61].
Other remarkable application of chiral bicyclic guanidine 22b is the enantioselective synthesis of axially chiral allenoates by the enantioselective isomerization of 3‐alkynoates (Scheme 3.34) [62].
Scheme 3.34. Enantioselective isomerization of 3‐alkynoate catalyzed by 22b.
Source: [62].
Ishikawa and co‐workers developed chiral monocyclic guanidine 23 having a hydroxy group, and applied the catalyst to the enantioselective Michael addition of glycine imines to acrylates (Scheme 3.35) [63]. The control experiments suggested that the matched relative configuration of the three chiral centers on the catalyst and the existence of the hydroxy group are essential for achieving both high conversion and high enantioselectivity. The catalyst was also applied to the enantioselective oxa‐Michael addition for the synthesis of chromane skeletons [64].